Cationic biocides are utilized in various biomedical products for their biocidal activity against a wide variety of microorganisms, as well as for their generally low toxicity in the applications for which they are used. Examples of cationic biocides include surface active quaternary ammonium compounds such as benzalkonium chloride and also polyquaternary ammonium compounds such as polyquaternium-1. Although cationic biocides are in widespread use as preservatives and antimicrobial agents in ophthalmic solutions and contact lens care solutions, they can have deleterious effects, and thus there are trade-offs associated with their use. For example, in any particular formulation a sufficient amount of the cationic biocide must be present to be effective in killing/inhibiting antimicrobial growth, yet not so much as to increase the potential for toxic effects and/or discomfort with normal use. In addition, cationic biocides, due to their ionic charge, may cause compatibility problems with other formulation components. For example, in complex formulations such as emulsions where droplet stability is critical, negatively charged droplets will aggregate in the presence of cationic molecules, thus limiting the use of this otherwise effective biocide class in these types of formulations.
Multipurpose solutions that can be used to clean, disinfect and condition lenses are available and are increasingly popular with contact lens users. Some multipurpose solutions may qualify as a “Chemical Disinfecting Solution” for use without rubbing, as opposed to conventional contact lens clearing or disinfecting solutions, which typically require a rubbing step in order to achieve a designated level of biocidal performance. Generally, these types of solutions would require a stronger level of biocidal activity, and thus either a more efficacious biocide or a higher concentration of biocide. In some instances, there is no requirement that these solutions be rinsed from the contact lens before being placed in the eye, and in other cases, the contact lens user may not always be diligent about rinsing their lenses prior to insertion, so that the solution may directly contact the ocular surface. In these types of formulations it is especially critical that the potential for toxic effects of cationic biocides be minimized.
A particular concern in case of soft contact lenses is the propensity of the biocide to be absorbed into hydrogel lens materials or adsorbed onto the lens surface, an effect commonly referred to as biocide “uptake”. Typically, uptake occurs as the lens resides in the lens care solution containing the biocide. After the lens is replaced into the eye, the absorbed biocide may then be released from the lens onto the eye tissue, with the potential for ongoing irritation of sensitive ocular tissues. As the lenses may be worn for some duration, this ongoing release may have the effect of amplifying any potentially toxic or irritating effects of the biocide, as the lens is then effectively acting as a reservoir for the continued release of the biocide.
It would be advantageous to provide compositions that contain a cationic biocide yet have a reduced degree of biocide uptake into hydrogel biomaterials such as contact lenses. In this way, compositions preserved with cationic biocides, including, for example, ophthalmic and lens care compositions intended for direct application to the eye and no-rub and other lens care solutions intended for use with soft contact lenses, could be safely used without concern for increased toxicity or discomfort. It would also be advantageous to use cationic biocides as preservatives for certain pharmaceutical emulsions without impacting droplet stability. The present invention is directed to achieving these aims.